Uy Gary D, Downs Karen M, Gardner Richard L
Mammalian Development Laboratory, University of Oxford, Department of Zoology, South Parks Road, Oxford, OX1 3PS, UK.
Development. 2002 Aug;129(16):3913-24. doi: 10.1242/dev.129.16.3913.
At the blastocyst stage of pre-implantation mouse development, close contact of polar trophectoderm with the inner cell mass (ICM) promotes proliferation of undifferentiated diploid trophoblast. However, ICM/polar trophectoderm intimacy is not maintained during post-implantation development, raising the question of how growth of undifferentiated trophoblast is controlled during this time. The search for the cellular basis of trophoblast proliferation in post-implantation development was addressed with an in vitro spatial and temporal analysis of fibroblast growth factor 4-dependent trophoblast stem cell potential. Two post-implantation derivatives of the polar trophectoderm - early-streak extra-embryonic ectoderm and late-streak chorionic ectoderm - were microdissected into fractions along their proximodistal axis and thoroughly dissociated for trophoblast stem cell culture. Results indicated that cells with trophoblast stem cell potential were distributed throughout the extra-embryonic/chorionic ectoderm, an observation that is probably attributable to non-coherent growth patterns exhibited by single extra-embryonic ectoderm cells at the onset of gastrulation. Furthermore, the frequency of cells with trophoblast stem cell potential increased steadily in extra-embryonic/chorionic ectoderm until the first somite pairs formed, decreasing thereafter in a manner independent of proximity to the allantois. Coincident with occlusion of the ectoplacental cavity via union between chorionic ectoderm and the ectoplacental cone, a decline in the frequency of mitotic chorionic ectoderm cells in vivo, and of trophoblast stem cell potential in vitro, was observed. These findings suggest that the ectoplacental cavity may participate in maintaining proliferation throughout the developing chorionic ectoderm and, thus, in supporting its stem cell potential. Together with previous observations, we discuss the possibility that fluid-filled cavities may play a general role in the development of tissues that border them.
在植入前小鼠发育的囊胚阶段，极性滋养外胚层与内细胞团（ICM）的紧密接触促进了未分化二倍体滋养层细胞的增殖。然而，在植入后发育过程中，ICM/极性滋养外胚层的紧密关系并未维持，这就引发了一个问题，即在这段时间内未分化滋养层细胞的生长是如何受到控制的。通过对成纤维细胞生长因子4依赖性滋养层干细胞潜能进行体外时空分析，研究了植入后发育中滋养层细胞增殖的细胞基础。极性滋养外胚层的两个植入后衍生物——早期原条外胚层和晚期原条绒毛膜外胚层——沿着其近端到远端轴被显微切割成几部分，并充分解离以进行滋养层干细胞培养。结果表明，具有滋养层干细胞潜能的细胞分布在整个外胚层/绒毛膜外胚层中，这一观察结果可能归因于原肠胚形成开始时单个外胚层细胞表现出的非连贯生长模式。此外，具有滋养层干细胞潜能的细胞频率在外胚层/绒毛膜外胚层中稳步增加，直到第一对体节形成，此后以与距尿囊的距离无关的方式下降。与绒毛膜外胚层和外胎盘锥结合导致外胎盘腔闭塞同时，观察到体内有丝分裂绒毛膜外胚层细胞的频率以及体外滋养层干细胞潜能均下降。这些发现表明，外胎盘腔可能参与维持整个发育中的绒毛膜外胚层的增殖，从而支持其干细胞潜能。结合先前的观察结果，我们讨论了充满液体的腔可能在与其相邻的组织发育中发挥普遍作用的可能性。
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